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2011 AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics
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2011 AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics
Science Photo Library
CRLX101 for advanced solid tumours
Published Online December 16, 2011 DOI:10.1016/S14702045(11)70392-8 The 2011 AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics was held on Nov 12–16, 2011, in San Francisco, CA, USA
Edward G Garmey (Cambridge, MA, USA) presented the results of a phase 1/2a study of CRLX101, a novel cyclodextrin-containing nanoparticle conjugate of topoisomerase 1 inhibitor camptothecin, in patients with advanced, pretreated solid tumours. In the phase 1 study, 24 patients received CRLX101 (intravenously over 1 h, every other week) at five escalating doses; on identification of a maximum tolerated dose (MTD; 15 mg/m2), a further 38 patients were enrolled at three centres in the phase 2a study. Overall median progressionfree survival (PFS) was 3·7 months for patients in the phase 2a study; median PFS for 21 patients with non-small-cell lung cancer (NSCLC) was 4·4 months, with 14 achieving stable disease for at least 3 months, and three for at least 6 months.
MABp1 for advanced cancers Blocking the activity of interleukin 1α could potentially interrupt the chronic inflammatory response that supports tumour growth and invasiveness. David S Hong (Houston, TX, USA) presented the results from the first group of a phase 1 trial of MABp1, a fully human monoclonal antibody (mAb) against interleukin 1α, in patients with advanced cancers. 36 patients were enrolled (four doses of MABp1 up to a maximum of 3·75 mg/kg, once every 3 weeks) and the treatment was well tolerated, with minimum adverse events. Enrolment in the second group, which will consist of the same highest dose administered every 2 weeks, is ongoing.
J1 for adults with cancer Joachim Gullbo (Uppsala, Sweden) presented a phase 1/2a study of intravenous melphalan-flufenamide (J1), a prodrug of melphalan activated 18
by the enzyme aminopeptidase N, in patients with advanced solid tumours (phase 1), advanced ovarian cancer or NSCLC (phase 2a). The recommended phase 2 dose (RP2D) was defined as 50 mg (fixed dose) every third week, after bone marrow suppression was identified as the dose-limiting toxicity in the dose-escalation phase, particularly in heavily pretreated patients. 40 patients were recruited in the phase 2a study; after three treatment cycles, two of 12 patients with ovarian carcinoma had progressive disease (PD), nine stable disease, and one partial response (PR), according to RECIST criteria. Three of 11 patients with NSCLC who were assessed had PD and eight stable disease.
Anti-ALK1 antiangiogenesis PF-03446962 is a fully human mAb against ALK1, a receptor for transforming growth factor β. It showed dose-dependent antiangiogenic activity in preclinical studies. Filippo de Braud (Milan, Italy) presented the results of a phase 1 study in patients with solid tumours. Eight doses (0·5–15 mg/kg) were assessed in 44 patients, leading to a RP2D of 6·75 kg/mg. Three patients had PRs and seven stable disease for at least 16 weeks, with manageable toxicities. Anti-ALK1 might be of particular interest for patients who have previously failed anti-VEGF therapy or treatment with VEGF receptor tyrosine kinase inhibitors.
BAY 86-9766 plus sorafenib for advanced cancer A phase 1 study presented as a poster by Neil J Clendeninn (Buffalo, NY, USA) and colleagues investigated BAY 86-9766, an investigational, highly selective MEK1/2 inhibitor, in combination with sorafenib, a small molecule, multikinase inhibitor. A doseescalation cohort of 32 patients with advanced metastatic or locally recurrent solid tumours received oral doses of BAY
86-9766 (5–50 mg, twice a day) and sorafenib (200 mg or 400 mg, twice a day) over a 28 day course (continued if treatment was beneficial). An additional 11 patients were enrolled in an MTD expansion cohort (50 mg BAY 86-9766, 400 mg sorafenib). Common adverse events included diarrhoea (89%) and rash (63%).
HSP90 inhibitor for recurrent or refractory cancer MPC-3100 is an inhibitor of HSP90, a chaperone that is important for the post-translational folding of proteins, many of which are necessary for the survival of cancer cells. Kyri Papandopoulos (San Antonio, TX, USA) presented the results of a phase 1 trial of oral MPC-3100 in patients with recurrent or refractory cancers. 26 patients received either daily doses (50–340 mg/m2) for 21 days followed by 7 days off; or twice daily doses of 240 mg or 320 mg for 28 days continuously. 12 (46%) patients achieved stable disease, with six (23%) remaining on the study for at least three cycles. Treatment was safe and tolerable at doses less than 600 mg/day.
Reolysin and chemotherapy In a phase 2 study, Anand B Karnad (San Antonio, TX, USA) and colleagues investigated wild-type reovirus (serotype 3, Reolysin, Oncolytics Biotech, Calgary, AB, Canada) in combination with paclitaxel and carboplatin in 14 patients with platinum-refractory recurrent or metastatic squamous cell cancers of the head and neck. Four of 13 patients who were assessed had PR and two stable disease for at least 12 weeks. Adverse events were mostly mild to moderate. An international, randomised, phase 3 trial of the combination treatment in the same population is now under way.
Neil Bennet www.thelancet.com/oncology Vol 13 January 2012
2011 AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics
Science Photo Library
CRLX101 for advanced solid tumours
Published Online December 16, 2011 DOI:10.1016/S14702045(11)70392-8 The 2011 AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics was held on Nov 12–16, 2011, in San Francisco, CA, USA
Edward G Garmey (Cambridge, MA, USA) presented the results of a phase 1/2a study of CRLX101, a novel cyclodextrin-containing nanoparticle conjugate of topoisomerase 1 inhibitor camptothecin, in patients with advanced, pretreated solid tumours. In the phase 1 study, 24 patients received CRLX101 (intravenously over 1 h, every other week) at five escalating doses; on identification of a maximum tolerated dose (MTD; 15 mg/m2), a further 38 patients were enrolled at three centres in the phase 2a study. Overall median progressionfree survival (PFS) was 3·7 months for patients in the phase 2a study; median PFS for 21 patients with non-small-cell lung cancer (NSCLC) was 4·4 months, with 14 achieving stable disease for at least 3 months, and three for at least 6 months.
MABp1 for advanced cancers Blocking the activity of interleukin 1α could potentially interrupt the chronic inflammatory response that supports tumour growth and invasiveness. David S Hong (Houston, TX, USA) presented the results from the first group of a phase 1 trial of MABp1, a fully human monoclonal antibody (mAb) against interleukin 1α, in patients with advanced cancers. 36 patients were enrolled (four doses of MABp1 up to a maximum of 3·75 mg/kg, once every 3 weeks) and the treatment was well tolerated, with minimum adverse events. Enrolment in the second group, which will consist of the same highest dose administered every 2 weeks, is ongoing.
J1 for adults with cancer Joachim Gullbo (Uppsala, Sweden) presented a phase 1/2a study of intravenous melphalan-flufenamide (J1), a prodrug of melphalan activated 18
by the enzyme aminopeptidase N, in patients with advanced solid tumours (phase 1), advanced ovarian cancer or NSCLC (phase 2a). The recommended phase 2 dose (RP2D) was defined as 50 mg (fixed dose) every third week, after bone marrow suppression was identified as the dose-limiting toxicity in the dose-escalation phase, particularly in heavily pretreated patients. 40 patients were recruited in the phase 2a study; after three treatment cycles, two of 12 patients with ovarian carcinoma had progressive disease (PD), nine stable disease, and one partial response (PR), according to RECIST criteria. Three of 11 patients with NSCLC who were assessed had PD and eight stable disease.
Anti-ALK1 antiangiogenesis PF-03446962 is a fully human mAb against ALK1, a receptor for transforming growth factor β. It showed dose-dependent antiangiogenic activity in preclinical studies. Filippo de Braud (Milan, Italy) presented the results of a phase 1 study in patients with solid tumours. Eight doses (0·5–15 mg/kg) were assessed in 44 patients, leading to a RP2D of 6·75 kg/mg. Three patients had PRs and seven stable disease for at least 16 weeks, with manageable toxicities. Anti-ALK1 might be of particular interest for patients who have previously failed anti-VEGF therapy or treatment with VEGF receptor tyrosine kinase inhibitors.
BAY 86-9766 plus sorafenib for advanced cancer A phase 1 study presented as a poster by Neil J Clendeninn (Buffalo, NY, USA) and colleagues investigated BAY 86-9766, an investigational, highly selective MEK1/2 inhibitor, in combination with sorafenib, a small molecule, multikinase inhibitor. A doseescalation cohort of 32 patients with advanced metastatic or locally recurrent solid tumours received oral doses of BAY
86-9766 (5–50 mg, twice a day) and sorafenib (200 mg or 400 mg, twice a day) over a 28 day course (continued if treatment was beneficial). An additional 11 patients were enrolled in an MTD expansion cohort (50 mg BAY 86-9766, 400 mg sorafenib). Common adverse events included diarrhoea (89%) and rash (63%).
HSP90 inhibitor for recurrent or refractory cancer MPC-3100 is an inhibitor of HSP90, a chaperone that is important for the post-translational folding of proteins, many of which are necessary for the survival of cancer cells. Kyri Papandopoulos (San Antonio, TX, USA) presented the results of a phase 1 trial of oral MPC-3100 in patients with recurrent or refractory cancers. 26 patients received either daily doses (50–340 mg/m2) for 21 days followed by 7 days off; or twice daily doses of 240 mg or 320 mg for 28 days continuously. 12 (46%) patients achieved stable disease, with six (23%) remaining on the study for at least three cycles. Treatment was safe and tolerable at doses less than 600 mg/day.
Reolysin and chemotherapy In a phase 2 study, Anand B Karnad (San Antonio, TX, USA) and colleagues investigated wild-type reovirus (serotype 3, Reolysin, Oncolytics Biotech, Calgary, AB, Canada) in combination with paclitaxel and carboplatin in 14 patients with platinum-refractory recurrent or metastatic squamous cell cancers of the head and neck. Four of 13 patients who were assessed had PR and two stable disease for at least 12 weeks. Adverse events were mostly mild to moderate. An international, randomised, phase 3 trial of the combination treatment in the same population is now under way.
Neil Bennet www.thelancet.com/oncology Vol 13 January 2012